Cohesin and CTCF complexes mediate contacts in chromatin loops depending on nucleosome positions

Attou, Aymen; Zülske, Tilo; Wedemann, Gero

doi:10.1016/j.bpj.2022.10.044

Cited by 6 publications

(3 citation statements)

References 106 publications

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“…These interactions include promoter-enhancer contacts that may result in the activation or repression of sets of genes or gene programs [1,2]. Several architectural proteins are involved in these mechanisms, including CTCF and the cohesin complex [3][4][5][6][7]. Actin has also emerged as an essential regulator of 3D genome organization [8][9][10][11].…”

Section: Introductionmentioning

confidence: 99%

Nuclear actin-dependent Meg3 expression suppresses metabolic genes by affecting the chromatin architecture at sites of elevated H3K27 acetylation levels

El Said,

Abdrabou,

Mahmood

et al. 2024

Preprint

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Three-dimensional organization of the eukaryotic genome is directly affected by the nuclear β-actin pool that regulates enhancer function by affecting H3K27 acetylation levels. This actin-based mechanism, in turn, influences enhancer-dependent transcriptional regulation and plays a crucial role in driving gene expression changes observed upon compartment-switching. Using a combination of bulk RNA-seq and qPCR analyses performed on total RNA from WT mouse embryonic fibroblasts (MEFs), β-actin heterozygous (HET) MEFs, and β-actin KO MEFs, in this study we demonstrate that expression of several lncRNAs is directly affected by β-actin depletion. Among these lncRNAs, Meg3 expression increases in a β-actin dosage-dependent manner. Using ChIRP-seq, ChIRP-MS and f RIP-qPCR, we show that β-actin depletion leads to alterations in Meg3 genomic association. It also leads to Meg3 enrichment at or close to gene regulatory sites including enhancers and promoters concomitantly with increased H3K27 acetylation levels. At these sites, specific Meg3 association with H3K27 acetylation leads to loss of promoter-enhancer interactions as revealed by the Activity by Contact (ABC) model that builds on RNA-seq, H3K27acetylation ChIP-seq, ATAC-seq and HiC-seq obtained in WT and β-actin KO MEFs. Results from metabolomics experiments in WT, HET and β-actin KO MEFs show these mechanisms contribute to the repression of genes involved in metabolic biosynthetic pathways for chondroitin, heparan, dermatan sulfate, and phospholipases, hence impacting their synthesis. We propose that at sites of actin-dependent increase in H3K27acetylation levels Meg3 interferes with promoter-enhancer interactions, potentially impairing local genome organization (or DNA looping) and negatively regulating gene expression.

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Section: Introductionmentioning

confidence: 99%

Nuclear actin-dependent Meg3 expression suppresses metabolic genes by affecting the chromatin architecture at sites of elevated H3K27 acetylation levels

El Said,

Abdrabou,

Mahmood

et al. 2024

Preprint

View full text Add to dashboard Cite

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“…Coarser models are necessary to perform simulations of the chromatin architecture on the size of tens of thousands, even millions of bp [31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50]. A mesoscale model developed by Schlick and coworkers [31,32] employed a rigid nucleosome core particle, flexible histone tails, and 9-bp-per-particle worm-like-chain linker DNA.…”

Section: Introductionmentioning

confidence: 99%

“…The 1CPN model proposed by Lequieu et al [38] uses a rigid nucleosome particle with a twistable wormlike chain representing linker DNA at the resolution of 3 bp per particle. Other coarse-grained models with nucleosome and subnucleosome resolution have also been developed in the past few years to connect the molecular and physicochemical data of nucleosomes with the mesoscale characteristics of chromatin, including the "beads-on-a-string" models from Wedemann's group [39][40][41][42][43] and Bajpai et al [44], the multiscale model from Farr et al [45], the rigid base-pair model from the van Noort group [46,47], the mesoscopic model from Zhurkin and Norouzi [48,49], and the multi-modal model from Orozco group [50,51]. Most of these mesoscopic models use one interaction site to represent a variable number of nucleotides, relinquishing from explicitly describing of the double helix, which is instead a fundamental determinant of the mechanical properties of DNA, and in particular its supercoiling behavior.…”

Section: Introductionmentioning

confidence: 99%

An associative memory Hamiltonian model for DNA and nucleosomes

Onuchic

Pierro

2023

PLoS Comput Biol

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A model for DNA and nucleosomes is introduced with the goal of studying chromosomes from a single base level all the way to higher-order chromatin structures. This model, dubbed the Widely Editable Chromatin Model (WEChroM), reproduces the complex mechanics of the double helix including its bending persistence length and twisting persistence length, and their respective temperature dependence. The WEChroM Hamiltonian is composed of chain connectivity, steric interactions, and associative memory terms representing all remaining interactions leading to the structure, dynamics, and mechanical characteristics of the B-DNA. Several applications of this model are discussed to demonstrate its applicability. WEChroM is used to investigate the behavior of circular DNA in the presence of positive and negative supercoiling. We show that it recapitulates the formation of plectonemes and of structural defects that relax mechanical stress. The model spontaneously manifests an asymmetric behavior with respect to positive or negative supercoiling, similar to what was previously observed in experiments. Additionally, we show that the associative memory Hamiltonian is also capable of reproducing the free energy of partial DNA unwrapping from nucleosomes. WEChroM is designed to emulate the continuously variable mechanical properties of the 10nm fiber and, by virtue of its simplicity, is ready to be scaled up to molecular systems large enough to investigate the structural ensembles of genes. WEChroM is implemented in the OpenMM simulation toolkits and is freely available for public use.

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Innovations in biophysics: A sampling of ideas celebrating Ned Seeman’s legacy

Schlick

2022

Biophysical Journal

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Cohesin and CTCF complexes mediate contacts in chromatin loops depending on nucleosome positions

Cited by 6 publications

References 106 publications

Nuclear actin-dependent Meg3 expression suppresses metabolic genes by affecting the chromatin architecture at sites of elevated H3K27 acetylation levels

Nuclear actin-dependent Meg3 expression suppresses metabolic genes by affecting the chromatin architecture at sites of elevated H3K27 acetylation levels

An associative memory Hamiltonian model for DNA and nucleosomes

Innovations in biophysics: A sampling of ideas celebrating Ned Seeman’s legacy

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